Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, Variants, or PubMed publications.

Have questions, comments, or suggestions? - Let us know!

Email us at : ckbsupport@genomenon.com

Gene VHL
Variant E70*
Impact List nonsense
Protein Effect loss of function - predicted
Gene Variant Descriptions VHL E70* results in a premature truncation of the Vhl protein at amino acid 70 of 213 (UniProt.org). E70* has not been characterized, however, due to the effects of other truncation mutations downstream of E70 (PMID: 14691445), is predicted to lead to a loss of Vhl protein function.
Associated Drug Resistance
Category Variants Paths

VHL mutant VHL inact mut VHL E70*

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Transcript NM_000551.4
gDNA chr3:g.10142055G>T
cDNA c.208G>T
Protein p.E70*
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_198156.2 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_000551.3 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_000551 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_001354723.1 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_000551.4 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_198156.3 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_198156 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38
NM_001354723.2 chr3:g.10142055G>T c.208G>T p.E70* RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows if any text in any cell matches the filter term
  • Use simple literal full or partial string matches
  • Separate multiple filter terms with a space. Any order may be used (i. e. a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page. Filtering has no impact on query parameters.
  • Use quotes to match on a longer phrase with spaces (i.e. "mtor c1483f")

Sorting

  • Generally, the default sort order for tables is set to be first column ascending; however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column. Be sure to set ascending or descending order for a given column before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
VHL inact mut renal cell carcinoma predicted - sensitive Alpha 2 Interferon + Bevacizumab Clinical Study - Cohort Actionable In a retrospective analysis, VHL alterations did not impact overall survival or objective response in renal cell carcinoma patients treated with a VEGF-targeted therapy, including Avastin (bevacizumab) and Alpha 2 Interferon combination therapy, but were associated with a prolonged time to progression (PMID: 16827904). 16827904
VHL inact mut pancreatic endocrine carcinoma sensitive Belzutifan FDA approved Actionable In a Phase II trial that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in an overall response rate of 80% (16/20, 1 complete response, 15 partial responses) in patients with Von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors harboring germline VHL mutations (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). detail... detail...
VHL inact mut hemangioblastoma sensitive Belzutifan FDA approved Actionable In a Phase II trial (LITESPARK-004) that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in an objective response rate of 44% (22/61, 4 complete responses, 18 partial responses) in patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma harboring germline VHL mutations, with a disease control rate of 90%, a median time to response of 5.4 months, and median progression-free survival not reached (J Clin Oncol 41, 2023 (suppl 16; abstr 2008); NCT03401788). detail... detail...
VHL inact mut hemangioblastoma sensitive Belzutifan Guideline Actionable Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma that do not require immediate surgery (NCCN.org). detail...
VHL inact mut clear cell renal cell carcinoma conflicting PT2399 Preclinical - Pdx Actionable In a preclinical study, PT2399 had variable impact on tumor growth in clear cell renal cell carcinoma (ccRCC) cell line and patient-derived xenograft (PDX) models with defective VHL, with decreased tumor growth in a VHL-defective ccRCC PDX model and some VHL-defective ccRCC cell line xenograft models, and no tumor suppression in other cell line xenograft models (PMID: 27595393). 27595393
VHL inact mut renal cell carcinoma predicted - sensitive Everolimus Case Reports/Case Series Actionable In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Afinitor (everolimus) had a trend towards improved in progression-free survival when stratified by the presence (median PFS=8.6 months, n=15) or absence (median PFS=5.5 months, n=16) of deleterious VHL mutations (PMID: 26951309). 26951309
VHL inact mut clear cell renal cell carcinoma not applicable N/A Guideline Risk Factor Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing clear cell renal cell carcinoma (NCCN.org). detail...
VHL inact mut islet cell tumor not applicable N/A Guideline Risk Factor Germline inactivating mutations in VHL result in von Hippel-Lindau (VHL) syndrome, which is associated with increased risk of developing pancreatic neuroendocrine tumors (NCCN.org). detail...
VHL inact mut renal cell carcinoma sensitive Belzutifan Guideline Actionable Welireg (belzutifan) is included in guidelines for patients with localized Von Hippel-Lindau disease-associated renal cell carcinoma harboring germline VHL mutations (PMID: 38788900; ESMO.org). detail... 38788900
VHL inact mut renal cell carcinoma sensitive Belzutifan FDA approved Actionable In a Phase II trial that supported FDA approval, Welireg (belzutifan) treatment was safe and resulted in a confirmed partial response (PR) in 36% (22/61) and unconfirmed PR in 11% (7/61) of patients with Von Hippel-Lindau disease-associated localized renal cell carcinoma harboring germline VHL mutations, median duration of response was not reached in responders (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). detail... detail...
VHL inact mut renal cell carcinoma sensitive Belzutifan Guideline Actionable Welireg (belzutifan) is included in guidelines for patients with Von Hippel-Lindau disease-associated renal cell carcinoma that do not require immediate surgery (NCCN.org). detail...
VHL inact mut renal cell carcinoma no benefit Apitolisib Case Reports/Case Series Actionable In a retrospective analysis from a Phase II clinical trial, patients with metastatic renal cell carcinoma treated with Apitolisib (GDC-0980) had no difference in progression-free survival when stratified by the presence (n=5) or absence (n=17) of deleterious VHL mutations (PMID: 26951309). 26951309
VHL inact mut renal cell carcinoma sensitive Pazopanib Phase II Actionable In a Phase II trial, Votrient (pazopanib) treatment resulted in an objective response rate of 42% (13/31, 13 partial responses) and stable disease in 58% of patients with Von Hippel-Lindau disease, with 75% (24/32) of the patients harboring confirmed VHL mutations; 52% (31/59, 2 complete and 29 partial responses) of target renal cell carcinomas responded to the treatment (PMID: 30236511; NCT01436227). 30236511
VHL inact mut renal cell carcinoma sensitive Pazopanib Guideline Actionable Votrient (pazopanib) is included in guidelines as systemic therapy for patients with renal cell carcinoma associated with Von Hippel-Lindau disease (NCCN.org). detail...
VHL inact mut retinal hemangioblastoma sensitive Belzutifan Phase II Actionable In a Phase II trial, Welireg (belzutifan) treatment was safe and resulted in an overall response rate of 32% (16/50, 1 complete response, 15 partial responses) in patients with Von Hippel-Lindau disease-associated CNS hemangioblastoma harboring germline VHL mutations, 69% (11/16) of patients with retinal hemangioblastoma experienced improvement (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 4555-4555; NCT03401788). detail...
VHL mutant islet cell tumor sensitive Belzutifan Guideline Actionable Welireg (belzutifan) is included in guidelines for patients with well-differentiated Grade 1/2 progressive pancreatic neuroendocrine tumors harboring germline VHL mutations (NCCN.org). detail...
VHL mutant renal cell carcinoma no benefit Unspecified VEGFR inhibitor Clinical Study - Meta-analysis Actionable In a meta-analysis of 6 clinical studies, VHL mutation status was not associated with overall response rate (relative risk=1.47, p=0.20), progression-free survival (HR=1.02, p=0.91), or overall survival (HR=0.80, p=0.21) in a total of 633 patients with renal cell carcinoma who received anti-VEGF therapies (PMID: 28103578). 28103578
VHL mutant renal cell carcinoma sensitive Everolimus Phase I Actionable In a Phase I study, Afinitor (everolimus), as compared to Apitolisib (GDC-0980), resulted in a greater progression free survival and overall survival in patients with renal cell carcinoma harboring VHL mutations (J Clin Oncol 32:5s, 2014 (suppl; abstr 4525)). detail...
VHL mutant renal cell carcinoma predicted - sensitive Sunitinib Phase I Actionable In a Phase I trial, 33% (6/18) of renal cell carcinoma patients harboring a VHL mutation, as determined from archived patient specimens, demonstrated a partial response when treated with Sutent (sunitinib) (PMID: 22105611). 22105611